CAR T Cells with Dual Targeting of CD19 and CD22 in Adult Patients with Recurrent or Refractory B Cell Malignancies: A Phase I Trial

Ten of 16 patients with large B cell lymphoma with progressive disease after CAR19 treatment had absent or low CD19.
[Nature Medicine]
Spiegel, J. Y., Patel, S., Muffly, L., Hossain, N. M., Oak, J., Baird, J. H., Frank, M. J., Shiraz, P., Sahaf, B., Craig, J., Iglesias, M., Younes, S., Natkunam, Y., Ozawa, M. G., Yang, E., Tamaresis, J., Chinnasamy, H., Ehlinger, Z., Reynolds, W., … Miklos, D. B. (2021). CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nature Medicine, 1–13. https://doi.org/10.1038/s41591-021-01436-0 Cite
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Depletion of High-Content CD14+ Cells from Apheresis Products Is Critical for the Successful Transduction and Expansion of CAR T Cells during Large-Scale cGMP Manufacturing

Investigators found that high CD14+ cell content posed a challenge for manufacturing CAR T cells especially in patients with non-Hodgkin’s lymphoma and multiple myeloma due to the non-specific phagocytosis of the magnetic beads used to activate CD3+ T cells.
[Molecular Therapy-Methods & Clinical Development]
Wang, X., Borquez-Ojeda, O., Stefanski, J., Du, F., Qu, J., Chaudhari, J., Thummar, K., Zhu, M., Shen, L., Hall, M., Gautam, P., Wang, Y., Senechal, B., Sikder, D., Adusumilli, P. S., Brentjens, R. J., Curran, K., Geyer, M. B., Mailankhody, S., … Rivière, I. (2021). Depletion of High-Content CD14+ Cells from Apheresis Products is Critical for the Successful Transduction and Expansion of CAR T cells during Large-scale cGMP Manufacturing. Molecular Therapy - Methods & Clinical Development, 0(0). https://doi.org/10.1016/j.omtm.2021.06.014 Cite
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Long-Term Activity of Tandem CD19/CD20 CAR Therapy in Refractory/Relapsed B-Cell Lymphoma: A Single-Arm, Phase I–II Trial

In this open-label, single-arm Phase I/II trial, 87 patients with recurrent/refractory non-Hodgkin lymphoma received an infusion at doses of 0.5 × 106–8 × 106 TanCAR7 T cells per kilogram of body weight after conditioning chemotherapy.
[Leukemia]
Zhang, Y., Wang, Y., Liu, Y., Tong, C., Wang, C., Guo, Y., Ti, D., Yang, Q., Qiao, S., Wu, Z., & Han, W. (2021). Long-term activity of tandem CD19/CD20 CAR therapy in refractory/relapsed B-cell lymphoma: a single-arm, phase 1–2 trial. Leukemia, 1–8. https://doi.org/10.1038/s41375-021-01345-8 Cite
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Circulating Tumor Cell Copy-Number Heterogeneity in ALK-Rearranged Non-Small-Cell Lung Cancer Resistant to ALK Inhibitors

Researchers provided in-depth investigation of copy number alteration heterogeneity in phenotypically characterized circulating tumor cells at resistance to Anaplastic Lymphoma Kinase (ALK)-tyrosine kinase inhibitors in ALK-positive non-small cell lung cancer.
[npj Precision Oncology]
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Extracellular Domain Shedding of the ALK Receptor Mediates Neuroblastoma Cell Migration

Investigators mapped the cleavage site to Asn654-Leu655 and demonstrated that cleavage inhibition of wild-type anaplastic lymphoma kinase significantly impeded neuroblastoma cell migration with subsequent prolongation of survival in mouse models.
[Cell Reports]
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Phase III Randomized Trial of Chemotherapy with or without Oblimersen in Older AML Patients: CALGB 10201 (Alliance)

Untreated older acute myeloid leukemia (AML) patients were randomized to cytarabine and daunorubicin followed by cytarabine consolidation with or without G3139. Addition of G3139 to chemotherapy failed to improve outcomes of older AML patients.
[Blood Advances]
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The BRD4 Inhibitor JQ1 Promotes Melanoma Cell Apoptosis by Regulating Mitochondrial Dynamics

Scientists showed that the bromodomain-containing protein 4 (BRD4) inhibitor JQ1 promoted the apoptosis of B16 melanoma cells by altering mitochondrial dynamics, thereby inducing mitochondrial dysfunction and increasing oxidative stress.
[Cancer Science]
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Multimodal Single-Cell Analysis of Cutaneous T Cell Lymphoma Reveals Distinct Sub-Clonal Tissue-Dependent Signatures

To identify and interrogate malignant clones in matched skin and blood from leukemic MF and SS patients, we combine T cell receptor clonotyping, with quantification of gene expression and cell surface markers at the single cell level.
[Blood]
Herrera, A., Cheng, A., Mimitou, E. P., Seffens, A., George, D. D., Bar-Natan, M., Heguy, A., Ruggles, K. V., Scher, J. U., Hymes, K., Latkowski, J.-A., Odum, N., Kadin, M. E., Ouyang, Z., Geskin, L., Smibert, P., Buus, T. B., & Koralov, S. (2021). Multimodal single-cell analysis of cutaneous T cell lymphoma reveals distinct sub-clonal tissue-dependent signatures. Blood, blood.2020009346. https://doi.org/10.1182/blood.2020009346 Cite
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The Alternative RelB NF-κB Subunit Is a Novel Critical Player in Diffuse Large B-Cell Lymphoma

The authors revealed a frequent activation of RelB in a large cohort of diffuse large B-cell lymphoma patients and cell lines, independently of their ABC or GCB subtypes.
[Blood]
Eluard, B., Nuan-Aliman, S., Faumont, N., Collares, D., Bordereaux, D., Montagne, A., Martins, I., Cagnard, N., Caly, M., Taoui, O., Lordello, L., Lehmann-Che, J., Tesson, B., Martinez-Climent, J.-A. A., Copie-Bergman, C., Haioun, C., Tilly, H., Bonsang, B., Vincent-Salomon, A., … Baud, V. I. (2021). The alternative RelB NF-κB subunit is a novel critical player in diffuse large B-cell lymphoma. Blood, blood.2020010039. https://doi.org/10.1182/blood.2020010039 Cite
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SPP1 Overexpression Is Associated with Poor Outcomes in ALK Fusion Lung Cancer Patients without Receiving Targeted Therapy

Scientists screened a total of 521 tumor specimens from Chinese patients with lung cancer for anaplastic lymphoma receptor tyrosine kinase fusion by immunohistochemistry and confirmed by fluorescence in situ hybridization.
[Scientific Reports]
Ji, X., Liu, Y., Mei, F., Li, X., Zhang, M., Yao, B., Wu, R., You, J., & Pei, F. (2021). SPP1 overexpression is associated with poor outcomes in ALK fusion lung cancer patients without receiving targeted therapy. Scientific Reports, 11(1), 14031. https://doi.org/10.1038/s41598-021-93484-2 Cite
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FoundationOne®CDx Receives FDA-Approval as a Companion Diagnostic for ALUNBRIG® (Brigatinib) to Identify Patients with ALK Positive Metastatic Non-Small Cell Lung Cancer

Foundation Medicine, Inc. announced that it has received approval from the US FDA for FoundationOne®CDx to be used as a companion diagnostic for ALUNBRIG®, which is currently FDA-approved for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer as detected by an FDA-approved test.
[Foundation Medicine, Inc.]
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